Delays and disruptions reduce the reliability and stability of the rail operations. Railway traffic rescheduling includes ways to manage the operations during and after the occurrences of such disturbances. In this study, we consider the simultaneous presence of large disruptions (temporary full or partial blockage of tracks) as well as stochastic variation of operations, as a source of disturbance. The occurrence time of blockage and its recovery time are given. We designed a simulation-based optimization model that incorporates dynamic dispatch priority rules with the objective of minimizing the total delay time of trains. We moreover design a variable neighborhood search meta-heuristic scheme for handling traffic under the limited capacity close to the blockage. The new plan includes a set of new departure times; dwell times, train running times. We evaluate the proposed model on a set of disruption scenarios covering a large part of the Iranian rail network. The result indicates that the developed simulation-based optimization approach has substantial advantages in producing practical solution quickly, when compared to commercial optimization software. In addition, the solutions have a lower average and smaller standard deviation than currently accepted solutions, determined by human dispatcher or by standard software packages.